Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal...Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.展开更多
Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The ai...Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD(23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase(DAO), pulmonary surfactant protein-A(SP-A), and C-reactive protein(CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase(MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB(NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and monocyte chemoattractant protein-1(MCP-1) were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4±585.5) U·L^(-1) vs(5626.4±795.1) U·L^(-1)], DAO[(1100.1±334.3) U·L^(-1) vs(1666.4±525.3) U·L^(-1)] and CRP [(7.6±1.2) μg·mL^(-1) vs(17.8±3.8) μg·mL^(-1)]. However, the serum SP-A concentration [(106.1±16.6) pg·mL^(-1) vs(90.1±14.9) pg·mL^(-1)] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to展开更多
文摘Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.
基金supported by the Key Research Lab of State Administration of Traditional ChineseComprehensive Investment Subject Construction Project of Tianjin Medical University(2016-2020)the National Natural Science Foundation of China(No.81703846)
文摘Modified Da-chai-hu Decoction(MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis(SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD(23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase(DAO), pulmonary surfactant protein-A(SP-A), and C-reactive protein(CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase(MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB(NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and monocyte chemoattractant protein-1(MCP-1) were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4±585.5) U·L^(-1) vs(5626.4±795.1) U·L^(-1)], DAO[(1100.1±334.3) U·L^(-1) vs(1666.4±525.3) U·L^(-1)] and CRP [(7.6±1.2) μg·mL^(-1) vs(17.8±3.8) μg·mL^(-1)]. However, the serum SP-A concentration [(106.1±16.6) pg·mL^(-1) vs(90.1±14.9) pg·mL^(-1)] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to
